Post-translational control of proteins through covalent attachment of ubiquitin plays important roles in all eukaryotic cell functions. The ubiquitin system in humans consists of 2 E1, 35 E2 and >600 E3 ubiquitin ligases as well as hundreds of deubiquitylases, which reverse ubiquitin attachment. Moreover, there are hundreds of proteins with ubiquitin-binding domains that bind one of the eight possible polyubiquitin chains. Dysfunction of the ubiquitin system is associated with many diseases such as cancer, autoimmunity and neurodegeneration, demonstrating the importance of ubiquitylation. Therefore, enzymes of the ubiquitin system are considered highly attractive drug targets. In recent years, mass spectrometry (MS)-based techniques have become increasingly important in the deciphering of the ubiquitin system. This short review addresses the state-of-the-art MS techniques for the identification of ubiquitylated proteins and their ubiquitylation sites. We also discuss the identification and quantitation of ubiquitin chain topologies and highlight how the activity of enzymes in the ubiquitin pathway can be measured. Finally, we present current MS tools that can be used for drug discovery in the ubiquitin space.
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Cover Image
Cover Image
The Holliday junction. The structure of the Holliday junction is highly variable, being adaptable to its biological function in recombination and to applications in biomolecular engineering. This image shows the how the junction extends from simple schematics to crystal structures as DNA only and in protein complexes. In addition, the junction has been exploited as an element in the design of 2-D and 3-D lattices in crystal engineering and more complex images and shapes through DNA origami. In this issue of Biochemical Society Transactions, P. Shing Ho reviews some interesting recent research on the Holliday junction; for details see pages 1149–1158.
Mass spectrometry techniques for studying the ubiquitin system
Rachel E. Heap, Megan S. Gant, Frederic Lamoliatte, Julien Peltier, Matthias Trost; Mass spectrometry techniques for studying the ubiquitin system. Biochem Soc Trans 15 October 2017; 45 (5): 1137–1148. doi: https://doi.org/10.1042/BST20170091
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